pectins and Atherosclerosis

Topics: Arteriosclerosis; Atherosclerosis; Carbohydrates; Humans; Hypercholesterolemia; Pectins

Galectin-3 is a carbohydrate-binding lectin, which has been implicated in the modulation of atherosclerotic pathophysiology, and is highly expressed in monocytes, macrophages and endothelial cells within atherosclerotic plaques. Modified citrus pectin (MCP) is produced from citrus pectin via pH and temperature modifications, which break it into shorter, non‑branched, galactose‑rich carbohydrate chains. MCP is able to tightly bind with galectin‑3, via recognition of its carbohydrate recognition domain, and facilitates the modulation of galectin‑3‑induced bioactivity. The present study explored the effects of MCP on the initiation of atherosclerosis. Eight‑week‑old apolipoprotein E‑deficient mice were treated with 1% MCP and fed an atherogenic diet for 4 weeks. The effects of MCP on atherosclerotic initiation were determined by pathological analysis and scanning electron microscope (SEM) imaging. MCP treatment reduced the size of atherosclerotic lesion areas, which was accompanied by decreased numbers of macrophages and smooth muscle cells (SMCs). Furthermore, SEM examination of the surface of the atheroma‑prone vessel wall indicated that MCP treatment reduced endothelial injury. To analyze the effects of MCP on monocyte adhesion, firstly, oxidized‑low density lipoprotein and various concentrations of MCP (0.025, 0.05, 0.1 and 0.25%) were incubated with the human umbilical vein endothelial cells (HUVECs) for stimulation and following this, the U937 cells were plated onto the HUVECs. The results revealed that MCP reduced the adhesion of U937 monocytes to HUVECs, indicating the adhesion-inhibiting effects of MCP. In conclusion, the present study revealed that MCP, a galectin‑3 inhibitor, reduced the size of atherosclerotic lesions by inhibiting the adhesion of leucocytes to endothelial cells. Inhibition of galectin‑3 function may be a therapeutic strategy for the treatment of atherosclerosis.

Topics: Animals; Apolipoproteins E; Atherosclerosis; Cells, Cultured; Diet; Disease Models, Animal; Endothelium, Vascular; Galectin 3; Human Umbilical Vein Endothelial Cells; Humans; Macrophages; Male; Mice; Mice, Knockout; Monocytes; Pectins; Plaque, Atherosclerotic

Atherosclerosis is a major risk factor for cardiovascular disease (CVD) and stroke. Galectin-3 is a carbohydrate-binding lectin implicated in the pathophysiology of CVD and is highly expressed within atherosclerotic lesions in mice and humans. The object of this present study was to use genetic deletion and pharmacological inhibition in a well-characterized mouse model of atherosclerosis to determine the role of galectin-3 in plaque development. Apolipoprotein-E/galectin-3 knockout mice were generated and fed a high-cholesterol "western" diet. Galectin-3 deletion had no consistent effect on the serum lipid profile but halved atherosclerotic lesion formation in the thoracic aorta (57% reduction), the aortic arch (50% reduction) and the brachiocephalic arteries. The aortic plaques were smaller, with reduced lipid core and less collagen. In apolipoprotein E-deficient (ApoE(-/-)) mice, there was a switch from high inducible nitric oxide expression in early lesions (6 weeks) to arginase-1 expression in later lesions (20 weeks), which was reversed in ApoE(-/-)/gal-3(-/-) mice. Administration of modified citrus pectin, an inhibitor of galectin-3, during the latter stage of the disease reduced plaque volume. We conclude that inhibiting galectin-3 causes decreased atherosclerosis. Strategies to inhibit galectin-3 function may reduce plaque progression and potentially represent a novel therapeutic strategy in the treatment of atherosclerotic disease.

Topics: Animals; Aorta, Thoracic; Apolipoproteins E; Arginase; Arginine; Atherosclerosis; Cell Line; Cell Movement; Fatty Acids, Nonesterified; Galectin 3; Humans; Macrophages; Mice; Mice, Inbred C57BL; Mice, Knockout; Pectins; Plaque, Atherosclerotic; Triglycerides; Weight Gain

A highly significant retardation of spontaneous atherosclerosis was observed in 2-year-old cockerels fed on a standard diet supplemented with 5 percent pectin for 18 months. The pectin-fed birds excreted three times as much lipid extract and almost twice as much cholesterol as did the control cockerels fed the standard diet supplemented with 5 percent nonnutritive fiber.

Topics: Animals; Arteriosclerosis; Atherosclerosis; Cellulose; Cholesterol; Diet; Dietary Fiber; Dietary Supplements; Fluids and Secretions; Lipids; Pectins; Pharmacology; Poultry Diseases; Research